An intriguing new study suggests that drastic diet and lifestyle changes may not only prevent the cognitive decline associated with Alzheimer's disease, but may also bring some improvement to people in the early stages of the disease.
The small, limited study differs from earlier findings that concluded that healthy lifestyle choices may lower risk but offer little hope of reversing the damage. The results have led co-authors of a paper published in June in the journal Alzheimer's Disease Research and Treatment to be more cautious and less excited.
“It was quite shocking to me, frankly, that we could get significant results on cognitive tests in just 50 patients, in just 20 weeks, just by making lifestyle changes. But it was striking in that it suggests that this might be important,” said lead author Rudolph Tanzi, the Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation at Harvard Medical School and co-director of the Massachusetts Comprehensive Neurodegenerative Disease Institute. “But I'll be the first to say that this is a small study. It was only 20 weeks, so let's not jump to any conclusions. But it's a great start.”
Stephen Arnold, professor of neurology at Massachusetts General Hospital and the E. Gerald Corrigan Professor of Alzheimer's Disease Therapeutic Sciences at Massachusetts General Hospital and lead author of the study, said the findings are promising but cautioned against “overinterpreting” them and would not recommend making sweeping diet or lifestyle changes based on the study alone.
“I think this is a well-done study. It just needs to be larger and longer,” Arnold said. “I hope people are intrigued and enthusiastic about the findings, but I don't want them to overinterpret them because we need more data.”
The trial pulled out all the stops in treating Alzheimer's disease, combining a range of interventions that, individually, may be effective in lowering risk. The researchers said the interventions were not only comprehensive, but also intensive, which they suggested may explain why results differed from previous studies that used more moderate interventions.
The 51 study participants, with an average age of 73.5 years, were in the early stages of Alzheimer's disease and all had been diagnosed with mild cognitive impairment or early dementia. 26 were randomly assigned to the intervention group and 25 to the control group.
intervention
The lifestyle followed by study participants in the intervention group
diet
All meals and snacks for subjects and their spouses were delivered to their respective homes.
The non-calorie-restricted vegan regimen was supplemented with supplements thought to support cognitive performance, including omega-3 fatty acids, curcumin, a multivitamin, vitamins C and B12, magnesium L-threonate, coenzyme Q, probiotics, and lion's mantle.
exercise
Participants did 30 minutes of aerobic exercise every day and strength training three times a week.
To reduce stress, the subjects spent an hour each day meditating, practicing yoga poses, stretching and breathing exercises under the supervision of a stress management expert.
Socialization
Participants attended hour-long support groups led by mental health professionals three times a week.
Participants in the intervention group were asked to follow a strict vegan diet for 20 weeks, with all meals and snacks delivered to the home of the subject or their spouse. The calorie-free diet was supplemented with supplements thought to support cognitive performance, including omega-3 fatty acids, curcumin, a multivitamin, vitamins C and B12, magnesium L-threonate, coenzyme Q, probiotics, and lions' mannequin.
These interventions were combined with 30 minutes of aerobic exercise each day and strength training three times a week. To reduce stress, participants also practiced meditation, yoga poses, stretching, and breathing exercises for one hour each day under the supervision of a stress management expert.
To enhance social support, subjects and their spouses attended hour-long support groups led by mental health professionals three times per week. In total, subjects received 12 hours of expert support per week via Zoom for the lifestyle intervention.
“Deep down, I think there's something real here.”
Steven Arnold
“I believe, wholeheartedly, that this is real,” said Arnold, chief of Translational Neurology at MGH and managing director of the center's Interdisciplinary Brain Center. “If we can significantly change the metabolism, inflammation and vascular environment of the body and brain, that's good for brain function. And this diet, exercise and stress reduction/socialization intervention may be as effective or more effective than the drugs we use for Alzheimer's.”
To establish a baseline and measure progress, participants took four standard tests used to measure cognitive ability in FDA drug trials. Results varied by test, but generally showed that the intervention group improved or showed no change, while the control group showed no change or worsening. For example, on the Clinical Global Impression of Change, after 20 weeks, 10 people (more than 40 percent) improved, 7 remained unchanged, 7 slightly worsened, and none moderately worsened. In contrast, in the control group, none improved, 8 remained unchanged, and 17 slightly or moderately worsened. The other two tests showed that the intervention group improved on average, while the control group worsened. On the fourth test, both groups worsened, with the control group worsening significantly more.
The researchers, from institutions in the US, UK, Finland and Sweden, also looked at the participants' blood and microbiome. One biomarker, called pTau 181, showed little change between the control and intervention groups, but the researchers saw improvement in another marker, which measures the ratio of two forms of amyloid beta protein that forms plaques in the brain, a hallmark of Alzheimer's disease.
The researchers found improvement in another marker, measuring the ratio of two forms of amyloid-beta protein that forms plaques in the brain, a hallmark of Alzheimer's disease.
Indicators related to cardiac and metabolic health, including cholesterol, A1c, and hemoglobin, also improved. The microbiome of the intervention group was altered, with increased populations of beneficial bacteria and decreased populations of bacteria thought to be associated with Alzheimer's disease. Furthermore, there was a dose-response effect in both biomarkers and cognitive tests, and the degree of change was positively correlated with adherence to the lifestyle intervention.
The study, funded by more than 20 private and charitable foundations, comes at a time of widespread optimism about Alzheimer's. After years of failed drug trials that left researchers wondering whether they really understood the disease, a study of 1,800 people over 18 months showed that a drug called lecanemab is the first treatment to slow the progression of Alzheimer's in people in the early stages of the disease, and it won FDA approval last year.
Tanji and Arnold acknowledged that the study's relatively small sample size was a limitation, but said a strength was that it was designed as a randomized controlled trial, which is considered the gold standard of science. The study was multimodal in design, but because so many different lifestyle factors were involved, it was difficult to disentangle the effects of each, said Tanji, who is also director of MGH's Genetics and Aging Research Unit and the Henry and Alison Mackens Center for Brain Health.
He and Arnold said the next step would be a larger study to see if the results could be replicated, and Arnold said one of the questions such a trial would answer is whether subjects would continue such an intensive intervention over the long term.
The conduct of the trial was significantly affected by the pandemic. Enrollment, which took place from 2018 to 2022, was still ongoing when COVID-19 hit in early 2020, but the initial enrollment goal of 100 participants was reduced. Distancing requirements forced researchers to move sessions online, which may have altered the effectiveness of the social support sessions. However, it was possible to expand the study population from a single site in San Francisco to other sites across the country, including Massachusetts General Hospital.
“This should be viewed as a pilot study, but the pilot data are important and strongly suggest that the lifestyle intervention was effective,” Tanzi said.
